Advanced therapies such as gene therapy, stem cells, tissue engineering are a paradigm shift in medicine: instead of traditional treatments administered throughout life to control symptoms, they can address disease at its origin through a single administration.
Over the last decade, Italy has made a significant contribution to this field: of the 17 advanced therapies authorised to date in the European Union, four resulted from Italian academic research. Strimvelis, the first ex-vivo gene therapy approved worldwide in 2016 for the treatment of a rare genetic immunodeficiency (ADA-SCID1) and Libmeldy, the first ex-vivo gene therapy for a rare neurodegenerative disease2 approved in 2020 for metachromatic leukodystrophy, were developed at the San Raffaele-Telethon Institute for Gene Therapy in Milan. Similarly, Holoclar, a tissue therapy approved in 2015 for corneal repair in limbal cell deficiency due to chemical or physical burns, was developed at the University of Modena and Reggio Emilia3. The list also includes Zalmoxis, a cell therapy for blood cancers devised by a spin-off of the San Raffaele Scientific Institute in Milan, that received a conditional approval from the European Medicines Agency (EMA) in 2016, then withdrawn in 2019 when better alternatives became available.
According to the latest report of the Alliance for Regenerative Medicine, by the end of 2020 there were more than 1,200 clinical trials of cell or tissue gene therapies under way worldwide, of which around 150 were already in phase 3. Academic research has proved able to generate innovative advanced therapies that improve the lives of patients. For this to continue to happen, however, key changes are needed.
First, studies must be designed from the outset in translational terms. If the aim is not simply to publish in prestigious journals, but to contribute to the development of therapies that can fill medical needs, even academic studies must comply with the requirements of the regulatory authorities, in order to avoid wasting time and money. The data collected and the production protocols must not only be scientifically valid, but also traceable and reproducible.
The success of drug development also depends on early, constructive dialogue with regulatory authorities. In this sense, the EMA has made a great effort to offer small and medium enterprises, and academia, a dedicated channel to encourage the development of innovative therapies where there is a medical need. For its part, the academia should strengthen its expertise in areas such as technology transfer, pharmaceutical development and regulatory affairs with specialised personnel, so as to help researchers enhance the value of their research and set it up with a clear view on how to reach the market. For Europe, this is an opportunity not to be missed. Other areas of the world, first and foremost North America, are investing in a structured and far-sighted manner in the development of this new type of potentially transformative drugs, for example by streamlining regulatory paths, introducing tax relief for clinical trials, and creating economic incentives for the accelerated review of products.
Another important factor is production, which currently represents a bottleneck in terms of cost and availability: for Italian and European academia to continue to contribute to the field, it must equip itself with GMP (Good Manufacturing Practice) grade facilities or obtain access to existing facilities on sustainable terms. The COVID-19 pandemic has clearly highlighted the negative impact of Europe's lack of manufacturing self-sufficiency, which in recent years has allowed the production of drugs to be relocated to lower-cost regions.
On the other hand, the pandemic has also shown how bureaucratic and administrative simplification of regulatory processes can speed up clinical research, a crucial aspect in a global emergency such as this, but also in the case of orphan diseases. In Italy, in particular, a task force of experts and a dedicated ethics committee have been set up by Agenzia Italiana del Farmaco and by the Lazzaro Spallanzani National Institute of Infectious Diseases, to assess all the COVID-19 studies submitted, in the same way as the EMA's Committee for Advanced Therapies (CAT) does at a central level. This has allowed consistent and competent assessments and constant international comparison. Even after the pandemic, these measures will remain crucial in such a specific and complex area as advanced therapies.
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Sessa et al, The Lancet, 388 (2016).
Rama P et al, N Engl J Med 363 (2010).